Publications

Surgical sutures are long-established medical devices that play an important role closing and healing damaged tissues and organs postoperatively. However, current commercial sutures are not able to detect infections at the wound site, which are quite frequent after surgery. In this work, we present mechanically stable smart sutures for the real-time monitoring of bacterial growth and biofilm formation. For this purpose, a conducting polymer named poly(3,4-ethylenedioxythiophene) (PEDOT), which is able to detect bacteria metabolites, was implemented as a coating onto commercial biostable sutures. A protecting hydrogel layer with adhesive properties, which was made of polydopamine-polyacrylamide (PDA-PAM), was used to prevent the detachment of the sensing coating of PEDOT upon looping and knotting the suture. The protective hydrogel preserved not only the knot mechanical properties of the suture but also the electrochemical response of the PEDOT-coating and, therefore, its ability to detect NADH from bacteria respiration. Ex-vivo assays using sutured swine intestine samples demonstrated that the suture with the PDA-PAM hydrogel layer detects the growth of bacteria in real tissues. As a proof of concept, sutures coated with PEDOT and protected with PDA-PAM were used to inhibit the local growth of bacteria in sutured intestines by applying controlled electrostimuli. Results evidenced that smart electro-responsive sutures can be used as multi-task devices focused on fighting bacterial infections, meaning not only monitoring but also hampering bacteria growth.

JTD Keywords: 4-ethylenedioxythiophene), Bacteria growth detection, Bacteria growth inhibition, Multi-task biomedical devices, Nanoparticles, Pape, Poly(3, Polydopamine-polyacrylamide, Sensor, Smart suture

Factor XII (FXII) is a zymogen present in blood that tends to adsorb onto the surfaces of blood-contacting medical devices. Once adsorbed, it becomes activated, initiating a cascade of enzymatic reactions that lead to surface-induced coagulation. This process is characterized by multiple redundancies, making it extremely challenging to prevent clot formation and preserve the properties of the surface. In this study, a novel modulatory coating system based on C1-esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII is proposed. Using surface plasmon resonance it is demonstrated that this coating system effectively repels blood plasma proteins, including FXII, while exhibiting high activity against activated FXII and plasma kallikrein under physiological conditions. This unique property enables the modulation of FXII activation without interfering with the overall hemostasis process. Furthermore, through dynamic Chandler loop studies, it is shown that this coating significantly improves the hemocompatibility of polymeric surfaces commonly used in medical devices. By addressing the root cause of contact activation, the synergistic interplay between the antifouling polymer brushes and the modulatory C1INH is expected to lay the foundation to enhance the hemocompatibility of medical device surfaces.© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.

JTD Keywords: adsorption, binding, c1-esterase-inhibitor, coatings, contact activation, factor-xii, fxii activation, hemocompatibility, hemocompatible surface modification, heparin, polymer brushes, system, thrombosis, Adsorption, Anticoagulation, Antifouling agent, Article, Beta-fxiia, Biocompatibility, Blood, Blood clotting, Blood clotting factor 12, Blood clotting factor 12a, Blood clotting factor 12a inhibitor, Blood coagulation, C1-esterase-inhibitor, Cell activation, Chemical activation, Coagulation, Coating (procedure), Complement component c1s inhibitor, Complement system, Controlled study, Dendrimers, Enzyme immobilization, Enzymes, Erythrocyte, Esters, Factor xii, Factor xii activation, Factor xiia, Fibrin deposition, Functional polymers, Fxii activation, Haemocompatibility, Hemocompatibility, Hemocompatible surface modification, Hemostasis, Heparin, Human, Hydrogel, Medical devices, Metabolism, Plasma kallikrein, Plasma protein, Plastic coatings, Platelet count, Polymer, Polymer brushes, Polymerization, Polymers, Property, Root cause, Surface plasmon resonance, Surface property, Surface reactions, Surface-modification, Thrombocyte adhesion, Β-fxiia

Neuroblastoma (NB) is a highly vascularized pediatric tumor arising from undifferentiated neural crest cells early in life, exhibiting both traditional endothelial-cell-driven vasculature and an intriguing alternative vasculature. The alternative vasculature can arise from cancer cells undergoing transdifferentiation into tumor-derived endothelial cells (TEC), a trait associated with drug resistance and tumor relapse. The lack of effective treatments targeting NB vasculature primarily arises from the challenge of establishing predictive in vitro models that faithfully replicate the alternative vasculature phenomenon. In this study, we aim to recreate the intricate vascular system of NB in an in vitro context, encompassing both types of vascularization, by developing a novel neuroblastoma-on-a-chip model. We designed a collagen I/fibrin-based hydrogel closely mirroring NB's physiological composition and tumor stiffness. This biomaterial created a supportive environment for the viability of NB and endothelial cells. Implementing a physiological shear stress value, aligned with the observed range in arteries and capillaries, within the microfluidic chip facilitated the successful development of vessel-like structures and triggered transdifferentiation of NB cells into TECs. The vascularized neuroblastoma-on-a-chip model introduced here presents a promising and complementary strategy to animal-based research with a significant capacity for delving into NB tumor biology and vascular targeting therapy.

JTD Keywords: 3d tumor model, Angiogenesis, Endothelial-cells, Microfluidic device, Neuroblastoma, Origi, Transdifferentiation, Tumor, Tumor-derived endothelial cells, Tumor-on-a-chip, Vasculature

Functional precision medicine (FPM) has emerged as a new approach to improve cancer treatment. Despite its potential, FPM assays present important limitations such as the number of cells and trained personnel required. To overcome these impediments, here we describe a novel microfluidic platform that can be used to perform FPM assays, optimizing the use of primary cancer cells and simplifying the process by using microfluidics to automatize the process.© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

JTD Keywords: Bioassay, Biological assay, Cancer treatment, Functional assays, Lab-on-a-chip devices, Microfluidics, Personalized medicine, Precision medicine

Many neurodegenerative diseases are identified but their causes and cure are far from being well-known. The problem resides in the complexity of the neural tissue and its location which hinders its easy evaluation. Although necessary in the drug discovery process, in vivo animal models need to be reduced and show relevant differences with the human tissues that guide scientists to inquire about other possible options which lead to in vitro models being explored. From organoids to organ-on-a-chips, 3D models are considered the cutting-edge technology in cell culture. Cell choice is a big parameter to take into consideration when planning an in vitro model and cells capable of mimicking both healthy and diseased tissue, such as induced pluripotent stem cells (iPSC), are recognized as good candidates. Hence, we present a critical review of the latest models used to study neurodegenerative disease, how these models have evolved introducing microfluidics platforms, 3D cell cultures, and the use of induced pluripotent cells to better mimic the neural tissue environment in pathological conditions.

JTD Keywords: 3d in vitro models, bioprinting, ipsc cell culture, microfluidic device, 3d in vitro models, Bioprinting, Blood-brain-barrier, Cerebral organoids, Culture model, Endothelial-cells, Expression profile, Extracellular-matrix, Ipsc cell culture, Microfluidic device, Neurodegenerative diseases, On-a-chip, Pluripotent stem-cells, Shear-stress, Substrate stiffness

Neurovascular catheter technology has rapidly evolved over the past decade. While performance characteristics are well known to the practitioner, the design features of these new-generation catheters and their implications on performance metrics remain a mystery to most clinicians due to the limited number of available resources. This knowledge gap hampers informed device choices and also limits collaboration between clinicians and engineers. To aid fellow neurointerventionalists, in this primer we have summarized the basic concepts of catheter design and construction.

JTD Keywords: catheter, device, Catheter, Device, Technology

Although multifunctional wearable devices have been widely investigated for healthcare systems, augmented/virtual realities, and telemedicines, there are few reports on multiple signal monitoring and logical signal processing by using one single nanomaterial without additional algorithms or rigid application-specific integrated circuit chips. Here, multifunctional intelligent wearable devices are developed using monolithically patterned gold nanowires for both signal monitoring and processing. Gold bulk and hollow nanowires show distinctive electrical properties with high chemical stability and high stretchability. In accordance, the monolithically patterned gold nanowires can be used to fabricate the robust interfaces, programmable sensors, on-demand heating systems, and strain-gated logical circuits. The stretchable sensors show high sensitivity for strain and temperature changes on the skin. Furthermore, the micro-wrinkle structures of gold nanowires exhibit the negative gauge factor, which can be used for strain-gated logical circuits. Taken together, this multifunctional intelligent wearable device would be harnessed as a promising platform for futuristic electronic and biomedical applications.© 2023 Wiley-VCH GmbH.

JTD Keywords: electronics, fabrication, intelligent multifunction, monolithic patterns, signal monitoring and processing, wearable devices, Gold nanowires, Intelligent multifunction, Intraocular-pressure, Monolithic patterns, Signal monitoring and processing, Wearable devices

JTD Keywords: Bacterial biofilms, Device, Growth, In-vitro, Infections, Laboratory method, Lung model, Responses, Temperature, Time

Muscular dystrophies are a heterogeneous group of highly debilitating diseases that result in muscle atrophy and weakness. The lack of suitable cellular and animal models that reproduce specific aspects of their pathophysiology is one of the reasons why there are no curative treatments for these disorders. This highlights a considerable gap between current laboratory models and clinical practice. We strongly believe that organs-on-chip could help to fill this gap. Organs-on-chip, and in particular muscles-on-chip, are microfluidic devices that integrate functional skeletal muscle tissues. Biosensors in these systems allow monitoring of muscle homeostasis or drug responses in situ. This Perspective outlines the potential of organs-on-chip as advanced models for muscular dystrophies, as well as the current challenges and future opportunities for this technology.© 2023. Published by The Company of Biologists Ltd.

JTD Keywords: cell, tissue, Animals, Lab-on-a-chip devices, Muscle, skeletal, Muscular dystrophies, Skeletal-muscle

The term 'mechanosensation' describes the capacity of cells to translate mechanical stimuli into the coordinated regulation of intracellular signals, cellular function, gene expression and epigenetic programming. This capacity is related not only to the sensitivity of the cells to tissue motion, but also to the decryption of tissue geometric arrangement and mechanical properties. The cardiac stroma, composed of fibroblasts, has been historically considered a mechanically passive component of the heart. However, the latest research suggests that the mechanical functions of these cells are an active and necessary component of the developmental biology programme of the heart that is involved in myocardial growth and homeostasis, and a crucial determinant of cardiac repair and disease. In this Review, we discuss the general concept of cell mechanosensation and force generation as potent regulators in heart development and pathology, and describe the integration of mechanical and biohumoral pathways predisposing the heart to fibrosis and failure. Next, we address the use of 3D culture systems to integrate tissue mechanics to mimic cardiac remodelling. Finally, we highlight the potential of mechanotherapeutic strategies, including pharmacological treatment and device-mediated left ventricular unloading, to reverse remodelling in the failing heart.© 2022. Springer Nature Limited.

JTD Keywords: cardiomyocyte proliferation, cross-linking, extracellular-matrix, focal adhesions, gene-expression, mechanical regulation, myocardial-infarction, substrate stiffness affects, t-cells, Ventricular assist device

This work presents the analytical physical modeling of undoped organic metal-electrolyte-semiconductor (OMES) capacitors in the framework of the Nernst-Planck-Poisson theory, including the presence of compact interfacial layers. This work derives an exact analytical solution, up to a quadrature, for the stationary electric potential and charge density distributions in both the semiconductor film and the electrolyte solution, and from them the sheet semiconductor charge and the stationary differential capacitance are obtained as a function of the applied voltage. The dependence of these magnitudes on the physical device parameters, like the ionic concentration of the electrolyte, the capacitance of the interfacial compact layers and the injected hole density is then analyzed. This work shows that ionic diffusive effects in the electrolyte can play an important role in the device response, inducing a broadening of the transition from the weak to the strong accumulation regimes. This fact can make that the strong accumulation regime is not achieved in OMES within the usual voltage operation range of these devices. The analytical solution is validated by means of finite element numerical calculations. The implications of the results obtained on the physics of electrolyte gated organic field effect transistors (EGOFETs) are discussed.

JTD Keywords: Analytical model, Equivalent-circuit model, Metal electrolyte semiconductor capacitors, Metal insulator semiconductor capacitors, Organic devices

The percutaneous device dilemma describes etiological factors, centered around the disrupted epithelial tissue surrounding non-remodelable devices, that contribute to rampant percutaneous device infection. Natural percutaneous organs, in particular their extracellular matrix mediating the “device”/epithelium interface, serve as exquisite examples to inspire longer lasting long-term percutaneous device design. For example, the tooth's imperviousness to infection is mediated by the epithelium directly surrounding it, the junctional epithelium (JE). The hallmark feature of JE is formation of hemidesmosomes, cell/matrix adhesive structures that attach surrounding oral gingiva to the tooth's enamel through a basement membrane. Here, the authors survey the multifaceted functions of the JE, emphasizing the role of the matrix, with a particular focus on hemidesmosomes and their five main components. The authors highlight the known (and unknown) effects dental implant – as a model percutaneous device – placement has on JE regeneration and synthesize this information for application to other percutaneous devices. The authors conclude with a summary of bioengineering strategies aimed at solving the percutaneous device dilemma and invigorating greater collaboration between clinicians, bioengineers, and matrix biologists. © 2022 The Authors

JTD Keywords: amino-acid-sequence, bioinspired surfaces, cell-secreted protein, growth-factor receptor, hemidesmosome, integrin beta-4 subunit, junctional epithelium, keratinocyte-derived chemokine, laminin-binding integrins, marginal bone loss, percutaneous device, percutaneous implant, pressure wound therapy, soft-tissue integration, Bioinspired surfaces, Bullous-pemphigoid antigen, Hemidesmosome, Junctional epithelium, Percutaneous device, Percutaneous implant

This manuscript presents portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0°, 90°, 180°, 270°) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia Coli at 1 MHz while applying a continuous flow of 5 ?L/min. Device functionalities were verified under different conditions achieving a 83% trapping efficiency in the best case. © Springer International Publishing Switzerland 2014.

JTD Keywords: bacteria, emulsifier, enterobacter, exopolysaccharide, Bacteria, Bacteria concentrations, Biochemical engineering, Cell concentrator, Class e amplifier, Class-e amplifier, Device functionality, Dielectrophoresis, Electronic equipment, Electronics, Electrophoresis, Emulsifier, Enterobacter, Escherichia coli, Exopolysaccharide, Inter-digitated electrodes, Lab-on-a-chip (loc), Low cost, Low costs, Low-cost electronics, Medical computing, Monosaccharide, Portable device, Power amplifiers, Trapping efficiencies

JTD Keywords: catheter, device, Catheter, Device, Thrombectomy

Flexible electrochemical sensors based on electroactive materials have emerged as powerful analytical tools for biomedical applications requiring bioanalytes detection. Within this context, 3D printing is a remarkable technology for developing electrochemical devices, due to no design constraints, waste minimization, and batch manufacturing with high reproducibility. However, the fabrication of 3D printed electrodes is still limited by the in-house fabrication of conductive filaments, which requires the mixture of the electroactive material with melted of thermoplastic polymer (e.g., polylactic acid, PLA). Herein, a simple approach is presented for preparing electrochemical dopamine (DA) biosensors. Specifically, the surface of 3D-printed PLA specimens, which exhibit an elastic modulus and a tensile strength of 3.7 +/- 0.3 GPa and 47 +/- 1 MPa, respectively, is activated applying a 0.5 m NaOH solution for 30 min and, subsequently, poly(3,4-ethylenedioxythiophene) is polymerized in situ using aqueous solvent. The detection of DA with the produced sensors has been demonstrated by cyclic voltammetry, differential pulse voltammetry, and chronoamperometry. In summary, the obtained results reflect that low-cost electrochemical sensors, which are widely used in medicine and biotechnology, can be rapidly fabricated using the proposed approach that, although based on additive manufacturing, does not require the preparation of conductive filaments.

JTD Keywords: 3d printers, Additive manufacturing, Amines, Batch manufacturing, Biomedical applications, Chronoamperometry, Conducting polymer, Conducting polymers, Conductive filaments, Conservation, Cyclic voltammetry, Differential pulse voltammetry, Electroactive material, Electrochemical biosensor, Electrochemical devices, Electrochemical sensors, Electrodes, Electron emission, Flexible electrode, High reproducibility, Medical applications, Neurophysiology, Poly-3 ,4-ethylenedioxythiophene, Polyesters, Polylactic aci, Sodium hydroxide, Tensile strength, Thermoplastic polymer

Organ-on-a-chip (OOC) devices offer new approaches for metabolic disease modeling and drug discovery by providing biologically relevant models of tissues and organs in vitro with a high degree of control over experimental variables for high-content screening applications. Yet, to fully exploit the potential of these platforms, there is a need to interface them with integrated non-labeled sensing modules, capable of monitoring, in situ, their biochemical response to external stimuli, such as stress or drugs. In order to meet this need, we aim here to develop an integrated technology based on coupling a localized surface plasmon resonance (LSPR) sensing module to an OOC device to monitor the insulin in situ secretion in pancreatic islets, a key physiological event that is usually perturbed in metabolic diseases such as type 2 diabetes (T2D). As a proof of concept, we developed a biomimetic islet-on-a-chip (IOC) device composed of mouse pancreatic islets hosted in a cellulose-based scaffold as a novel approach. The IOC was interfaced with a state-of-the-art on-chip LSPR sensing platform to monitor the in situ insulin secretion. The developed platform offers a powerful tool to enable the in situ response study of microtissues to external stimuli for applications such as a drug-screening platform for human models, bypassing animal testing.

JTD Keywords: biosensor, cytoarchitecture, dna hybridization, gelatin, in situ insulin monitoring, langerhans, lspr sensors, microfluidic device, organ-on-a-chip, parallel, platform, scaffold, Animals, Biosensing techniques, Diabetes mellitus, type 2, Drug discovery, Drug evaluation, preclinical, Human pancreatic-islets, Humans, In situ insulin monitoring, Insulin secretion, Insulins, Lab-on-a-chip devices, Lspr sensors, Oligonucleotide array sequence analysis, Organ-on-a-chip, Surface plasmon resonance

© 2020 Wiley-VCH GmbH Probing nanoscale electrical properties of organic semiconducting materials at the interface with an electrolyte solution under externally applied voltages is key in the field of organic bioelectronics. It is demonstrated that the conductivity and interfacial capacitance of the active channel of an electrolyte-gated organic field-effect transistor (EGOFET) under operation can be probed at the nanoscale using scanning dielectric microscopy in force detection mode in liquid environment. Local electrostatic force versus gate voltage transfer characteristics are obtained on the device and correlated with the global current–voltage transfer characteristics of the EGOFET. Nanoscale maps of the conductivity of the semiconducting channel show the dependence of the channel conductivity on the gate voltage and its variation along the channel due to the space charge limited conduction. The maps reveal very small electrical heterogeneities, which correspond to local interfacial capacitance variations due to an ultrathin non-uniform insulating layer resulting from a phase separation in the organic semiconducting blend. Present results offer insights into the transduction mechanism at the organic semiconductor/electrolyte interfaces at scales down to ≈100 nm, which can bring substantial optimization of organic electronic devices for bioelectronic applications such as electrical recording on excitable cells or label-free biosensing.

JTD Keywords: Atomic force microscopy, Bioelectronic devices, Electrolyte gated organic field effect transistors, In-liquid scanning dielectric microscopy, Organic semiconducting blend

After a stroke, a great number of patients experience persistent motor impairments such as hemiparesis or weakness in one entire side of the body. As a result, the lack of use of the paretic limb might be one of the main contributors to functional loss after clinical discharge. We aim to reverse this cycle by promoting the use of the paretic limb during activities of daily living (ADLs). To do so, we describe the key components of a system composed of a wearable bracelet (i.e., a smartwatch) and a mobile phone, designed to bring a set of neurorehabilitation principles that promote acquisition, retention and generalization of skills to the home of the patient. A fundamental question is whether the loss in motor function derived from learned–non–use may emerge as a consequence of decision–making processes for motor optimization. Our system is based on well-established rehabilitation strategies that aim to reverse this behaviour by increasing the reward associated with action execution and implicitly reducing the expected cost of using the paretic limb, following the notion of reinforcement–induced movement therapy (RIMT). Here we validate an accelerometer-based measure of arm use and its capacity to discriminate different activities that require increasing movement of the arm. The usability and acceptance of the device as a rehabilitation tool is tested using a battery of self–reported and objective measurements obtained from acute/subacute patients and healthy controls. We believe that an extension of these technologies will allow for the deployment of unsupervised rehabilitation paradigms during and beyond hospitalization time. © 2021, Springer Nature Switzerland AG.

JTD Keywords: adls, hemiparesis, learned non-use, wearables, Activities of daily living, Adls, Functional loss, Generalisation, Hemiparesis, Learned non-use, Motor impairments, Neurorehabilitation [], Patient experiences, Stroke, Wearable devices, Wearable technology, Wearables

Many studies have focused on novel noninvasive techniques to monitor respiratory rate such as bioimpedance. We propose an algorithm to detect respiratory phases using wearable bioimpedance to compute time parameters like respiratory rate, inspiratory and expiratory times, and duty cycle. The proposed algorithm was compared with two other algorithms from literature designed to estimate the respiratory rate using physiological signals like bioimpedance. We acquired bioimpedance and airflow from 50 chronic obstructive pulmonary disease (COPD) patients during an inspiratory loading protocol. We compared performance of the algorithms by computing accuracy and mean average percentage error (MAPE) between the bioimpedance parameters and the reference parameters from airflow. We found similar performance for the three algorithms in terms of accuracy (>0.96) and respiratory time and rate errors (<3.42 %). However, the proposed algorithm showed lower MAPE in duty cycle (10.18 %), inspiratory time (10.65 %) and expiratory time (8.61 %). Furthermore, only the proposed algorithm kept the statistical differences in duty cycle between COPD severity levels that were observed using airflow. Accordingly, we suggest bioimpedance to monitor breathing pattern parameters in home situations.Clinical relevance - This study exhibits the suitability of wearable thoracic bioimpedance to detect respiratory phases and to compute accurate breathing pattern parameters. © 2021 IEEE.

JTD Keywords: algorithms, copd, signals, Algorithm, Algorithms, Bioimpedance, Breathing rate, Chronic obstructive lung disease, Electronic device, Human, Humans, Lung, Pulmonary disease, chronic obstructive, Respiratory rate, Wearable electronic devices

Herein, a facile approach toward transforming a 2D polypropylene flexible mesh material into a 4D dynamic system is presented. The versatile platform, composed by a substrate of knitted fibers of isotactic polypropylene (iPP) mesh and a coating of thermosensitive poly(N‐isopropylacrylamide‐co‐N,N’‐methylene bis(acrylamide) (PNIPAAm‐co‐MBA) hydrogel, covalently bonded to the mesh surface, after cold‐plasma surface treatment and radical polymerization, is intended to undergo variations in its geometry via its reversible folding/unfolding behavior. The study is the first to trace the 3D movement of a flat surgical mesh, intended to repair hernia defects, under temperature and humidity control. An infrared thermographic camera and an optical microscope are used to evaluate the macroscopic and microscopic structure stimulus response. The presence of the PP substrate and the distribution of the gel surrounding the PP threads, affect both the PNIPAAM gel expansion/contraction as well as the time of folding/unfolding response. Furthermore, PP‐g‐PNIPAAm meshes show an increase in the bursting strength of ≈16% with respect to the uncoated mesh, offering a strongest and adaptable system for its future implantation in human body. The findings reported offer unprecedented application possibilities in the biomedical field.

JTD Keywords: Dynamic devices, Polypropylene meshes, Surgical implants, Thermosensitive hydrogels

The use of wearable devices in clinical routines could reduce healthcare costs and improve the quality of assessment in patients with chronic respiratory diseases. The purpose of this study is to evaluate the capacity of a Shimmer3 wearable device to extract reliable cardiorespiratory parameters from surface diaphragm electromyography (EMGdi). Twenty healthy volunteers underwent an incremental load respiratory test whilst EMGdi was recorded with a Shimmer3 wearable device (EMGdiW). Simultaneously, a second EMGdi (EMGdiL), inspiratory mouth pressure (Pmouth) and lead-I electrocardiogram (ECG) were recorded via a standard wired laboratory acquisition system. Different cardiorespiratory parameters were extracted from both EMGdiW and EMGdiL signals: heart rate, respiratory rate, respiratory muscle activity and mean frequency of EMGdi signals. Alongside these, similar parameters were also extracted from reference signals (Pmouth and ECG). High correlations were found between the data extracted from the EMGdiW and the reference signal data: heart rate (R = 0.947), respiratory rate (R = 0.940), respiratory muscle activity (R = 0.877), and mean frequency (R = 0.895). Moreover, similar increments in EMGdiW and EMGdiL activity were observed when Pmouth was raised, enabling the study of respiratory muscle activation. In summary, the Shimmer3 device is a promising and cost-effective solution for the ambulatory monitoring of respiratory muscle function in chronic respiratory diseases.

JTD Keywords: Cardiorespiratory monitoring, Chronic respiratory diseases, Fixed sample entropy, Non-invasive respiratory monitoring, Surface diaphragm electromyography, Wearable wireless device

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrPC-overexpressing mice.

JTD Keywords: Amyloid spreading, Microfluidic devices, Prnp, Synuclein

Commercialisation of emerging technological innovations such as medical devices can be a time-consuming and lengthy process resulting in a market entrance failure. To tackle this general problem, major challenges are being analysed, principally focusing on the role of Communities of Practitioners (CoPs) in the process of effective transfer of high-value emerging technologies from academia to market. Taking a case study approach, this document describes the role of a cross-disciplinary CoP in the technology transfer process within a convergence scenario. The case presented is a sensor array for ischemia detection developed by different practitioners from diverse organisations: university, research institution, hospital, and a scientific park. The analysis also involves the innovation ecosystem where all stakeholders are taken into account. This study contributes to a better understanding of the managerial implications of CoP fostering technology transfer and innovation, principally focused on the current need for new biomedical technologies and tools.

JTD Keywords: CoP, Medical devices, Innovation, Technology transfer, Ischemia

The present paper reports a bacteria autonomous controlled concentrator prototype with a user-friendly interface for bench-top applications. It is based on a micro-fluidic lab-on-a-chip and its associated custom instrumentation, which consists in a dielectrophoretic actuator, to pre-concentrate the sample, and an impedance analyser, to measure concentrated bacteria levels. The system is composed by a single micro-fluidic chamber with interdigitated electrodes and a instrumentation with custom electronics. The prototype is supported by a real-time platform connected to a remote computer, which automatically controls the system and displays impedance data used to monitor the status of bacteria accumulation on-chip. The system automates the whole concentrating operation. Performance has been studied for controlled volumes of Escherichia coli (E. coli) samples injected into the micro-fluidic chip at constant flow rate of 10 μL/min. A media conductivity correcting protocol has been developed, as the preliminary results showed distortion of the impedance analyser measurement produced by bacterial media conductivity variations through time. With the correcting protocol, the measured impedance values were related to the quantity of bacteria concentrated with a correlation of 0.988 and a coefficient of variation of 3.1%. Feasibility of E. coli on-chip automated concentration, using the miniaturized system, has been demonstrated. Furthermore, the impedance monitoring protocol had been adjusted and optimized, to handle changes in the electrical properties of the bacteria media over time.

JTD Keywords: Autonomous Device, Bacteria Concentrator, Dielectrophoresis, Escherichia coli, Impedance Analysis

This manuscript presents a portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0°, 90°, 180°, 270°) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia coli (E. coli) at 1 MHz while applying a continuous flow of 5 µL/min. The device functionalities were verified under different conditions, achieving an 83% trapping efficiency when counter-phased signals are used.

JTD Keywords: Cell Concentrator, Class E amplifier, Dielectrophoresis, Electronics, Lab-on-a-chip (LOC), Low cost, Portable device

Incorporating molecular switches as the active components in nanoscale electrical devices represents a current challenge in molecular electronics. It demands key requirements that need to be simultaneously addressed including fast responses to external stimuli and stable attachment of the molecules to the electrodes while mimicking the operation of conventional electronic components. Here, we report a single-molecule switching device that responds electrically to optical and chemical stimuli. A light pointer or a chemical signal can rapidly and reversibly induce the isomerization of bifunctional spiropyran derivatives in the bulk reservoir and, consequently, switch the electrical conductivity of the single-molecule device between a low and a high level. The spiropyran derivatives employed are chemically functionalized such that they can respond in fast but practical time scales. The unique multistimuli response and the synthetic versatility to control the switching schemes of this single-molecule device suggest spiropyran derivatives as key candidates for molecular circuitry.

JTD Keywords: Molecular Electronics, Multi-Responsive Molecular Switches, Photo- and Chemo-Switches Spiropyran, Single-Molecule Conductance, STM Break-Junction, Electronic equipment, Isomerization, Molecular electronics, Photochromism, Electrical conductivity, Electronic component, Molecular switches, Single-molecule conductances, Single-molecule devices, Spiropyran derivatives, Spiropyrans, STM Break-Junction, Molecules

Understanding how charges move through and between biomolecules is a fundamental question that constitutes the basis for many biological processes. On the other hand, it has potential applications in the design of sensors based on biomolecules and single molecule devices. In this review we introduce the study of the electron transfer (ET) process in biomolecules, providing an overview of the fundamental theory behind it and the different experimental approaches. The ET in proteins is introduced by reviewing a complete electronic characterization of a redox protein (azurin) using electrochemical scanning tunnelling microscopy (ECSTM). The ET process in DNA is overviewed and results from different experimental approaches are discussed. Finally, future directions in the study of the ET process in biomolecules are introduced as well as examples of possible technological applications.

JTD Keywords: Bioelectrochemistry, Biomolecular electronics, Charge transfer, Nanobiodevice, Single-molecule junction

Poly(vinylchloride) (PVC) is the most common polymer matrix used in the fabrication of ion-selective electrodes (ISEs). However, the surfaces of PVC-based sensors have been reported to show membrane instability. In an attempt to overcome this limitation, here we developed two alternative methods for the preparation of highly stable and robust ion-selective sensors. These platforms are based on the selective electropolymerization of poly(3,4-ethylenedioxythiophene) (PEDOT), where the sulfur atoms contained in the polymer covalently interact with the gold electrode, also permitting controlled selective attachment on a miniaturized electrode in an array format. This platform sensor was improved with the crosslinking of the membrane compounds with poly(ethyleneglycol) diglycidyl ether (PEG), thus also increasing the biocompatibility of the sensor. The resulting ISE membranes showed faster signal stabilization of the sensor response compared with that of the PVC matrix and also better reproducibility and stability, thus making these platforms highly suitable candidates for the manufacture of robust implantable sensors.

JTD Keywords: Biomedicine, Electrochemistry, Endoscope, Implantable device, Ion-selective electrode (ISE) sensor, Ischemia, pH detection, Biocompatibility, Chemical sensors, Electrochemistry, Electrodes, Electropolymerization, Endoscopy, Functional polymers, Implants (surgical), Ion selective electrodes, Medical applications, Polyvinyl chlorides, Stabilization, Biomedical applications, Biomedicine, Implantable devices, Ion selective sensors, Ischemia, Membrane instability, pH detection, Poly(3 ,4 ethylenedioxythiophene) (PEDOT), Ion selective membranes

Here we have developed a simple method for the fabrication of disposable implantable all-solid-state ion-selective electrodes (ISE) in an array format without using complex fabrication equipment or clean room facilities. The electrodes were designed in a needle shape instead of planar electrodes for a full contact with the tissue. The needle-shape platform comprises 12 metallic pins which were functionalized with conductive inks and ISE membranes. The modified microelectrodes were characterized with cyclic voltammetry, scanning electron microscope (SEM), and optical interferometry. The surface area and roughness factor of each microelectrode were determined and reproducible values were obtained for all the microelectrodes on the array. In this work, the microelectrodes were modified with membranes for the detection of pH and nitrate ions to prove the reliability of the fabricated sensor array platform adapted to an endoscope.

JTD Keywords: Chemical sensors, Cyclic voltammetry, Electrochemistry, Endoscopy, Fabrication, Implants (surgical), Microelectrodes, Needles, Nitrates, Scanning electron microscopy, Biomedicine, Fabricated sensors, Fabrication equipment, Implantable devices, Implantable sensors, Optical interferometry, Planar electrode, Roughness factor, Ion selective electrodes

This chapter contains sections titled: * Introduction * Biomedical Devices for In Vivo Analysis * Conclusions and Final Recommendations * References

JTD Keywords: Technology transfer, Innovation management, Nanotechnology, Nanobiosensor, Diabetes, Biomedical device, Implantable biosensors

This manuscript presents portable and low cost electronic system for specific point-of-use dielectrophoresis applications. The system is composed of two main modules: a) a multiphase generator based on a Class E amplifier, which provides 4 sinusoidal signals (0º, 90º, 180º, 270º) at 1 MHz with variable output voltage up to 10 Vpp (Vm) and an output driving current of 1 A; and b) a dielectrophoresis-based microfluidic chip containing two interdigitated electrodes. The system has been validated by concentrating Escherichia Coli at 1 MHz while applying a continuous flow of 5 μL/min. Device functionalities were verified under different conditions achieving a 83% trapping efficiency in the best case.

JTD Keywords: Cell Concentrator, Class E amplifier, Dielectrophoresis, Electronics, Lab-on-a-chip (LOC), Low cost, Portable device

Even if the performance of a given ventilator has been evaluated in the laboratory under very well controlled conditions, inappropriate maintenance and lack of long-term stability and accuracy of the ventilator sensors may lead to ventilation errors in actual clinical practice. The aim of this study was to evaluate the actual performances of ventilators during clinical routines. A resistance (7.69 cmH(2)O/L/s) - elastance (100 mL/cmH(2)O) test lung equipped with pressure, flow, and oxygen concentration sensors was connected to the Y-piece of all the mechanical ventilators available for patients in four intensive care units (ICUs; n = 66). Ventilators were set to volume-controlled ventilation with tidal volume = 600 mL, respiratory rate = 20 breaths/minute, positive end-expiratory pressure (PEEP) = 8 cmH(2)O, and oxygen fraction = 0.5. The signals from the sensors were recorded to compute the ventilation parameters. The average standard deviation and range (min-max) of the ventilatory parameters were the following: inspired tidal volume = 607 36 (530-723) mL, expired tidal volume = 608 36 (530-728) mL, peak pressure = 20.8 2.3 (17.2-25.9) cmH(2)O, respiratory rate = 20.09 0.35 (19.5-21.6) breaths/minute, PEEP = 8.43 0.57 (7.26-10.8) cmH(2)O, oxygen fraction = 0.49 0.014 (0.41-0.53). The more error-prone parameters were the ones related to the measure of flow. In several cases, the actual delivered mechanical ventilation was considerably different from the set one, suggesting the need for improving quality control procedures for these machines.

JTD Keywords: Equipment and supplies, Medical devices, Intravenous, Quality assurance, Health care quality assessment, Ventilator accuracy, Ventilation error

The achievement of a higher degree of integration of components – especially micropumps and power sources – is a challenge currently being pursued to obtain portable and totally autonomous microfluidic devices. This paper presents the integration of a micro direct methanol fuel cell (mDMFC) in a microfluidic platform as a smart solution to provide both electrical and pumping power to a Lab-on-a-Chip system. In this system the electric power produced by the fuel cell is available to enable most of the functionalites required by the microfluidic chip, while the generated CO2 from the electrochemical reaction produces a pressure capable of pumping a liquid volume through a microchannel. The control of the fuel cell operating conditions allows regulation of the flow rate of a liquid sample through a microfluidic network. The relation between sample flow rate and the current generated by the fuel cell is practically linear, achieving values in the range of 4–18 mL min 1 while having an available power between 1–4 mW. This permits adjusting the desired flow rate for a given application by controlling the fuel cell output conditions and foresees a fully autonomous analytical Lab-on-a-Chip in which the same device would provide the electrical power to a detection module and at the same time use the CO2 pumping action to flow the required analytes through a particular microfluidic design.

JTD Keywords: micro direct methanol fuel cell (mDMFC), Lab-on-a-chip (LOC), Microfluidic device

This article reports on the research and development of a cutting-edge biomedical device for continuous in-vivo glucose monitoring. This entirely public-funded process of technological innovation has been conducted at the University of Barcelona within a context of converging technologies involving the fields of medicine, physics, chemistry, biology, telecommunications, electronics and energy. The authors examine the value chain and the market challenges faced by in-vivo implantable biomedical devices based on nanotechnologies. In so doing, they trace the process from the point of applied research to the final integration and commercialization of the product, when the social rate of return from academic research can be estimated. Using a case-study approach, the paper also examines the high-tech activities involved in the development of this nano-enabled device and describes the technology and innovation management process within the value chain conducted in a University-Hospital-Industry-Administration-Citizens framework. Here, nanotechnology is seen to represent a new industrial revolution, boosting the biomedical devices market. Nanosensors may well provide the tools required for investigating biological processes at the cellular level in vivo when embedded into medical devices of small dimensions, using biocompatible materials, and requiring reliable and targeted biosensors, high speed data transfer, safely stored data, and even energy autonomy.

JTD Keywords: Biomedical device, Diabetes, Innovation management, Nanobiosensor, Nanotechnology, Research commercialization, Technology transfer, Academic research, Applied research, Barcelona, Biocompatible materials, Biological process, Biomedical analysis, Biomedical devices, Cellular levels, Converging technologies, Glucose monitoring, High-speed data transfer, Implantable biomedical devices, Implantable devices, In-vivo, Industrial revolutions, Innovation management, Medical Devices, Nanobiosensor, Rate of return, Research and development, Technological innovation, Value chains, Biological materials, Biomedical engineering, Biosensors, Commerce, Data transfer, Earnings, Engineering education, Glucose, Implants (surgical), Industrial research, Innovation, Medical problems, Nanosensors, Nanotechnology, Technology transfer, Equipment

Biosensors' research filed has clearly been changing towards the production of multifunctional and innovative design concepts to address the needs related with sensitivity and selectivity of the devices. More recently, waveguide biosensors, that do not require any label procedure to detect biomolecules adsorbed on its surface, have been pointed out as one of the most promising technologies for the production of biosensing devices with enhanced performance. Moreover the combination of optical and electrochemical measurements through the integration of transparent and conducting oxides in the multilayer structures can greatly enhance the biosensors' sensitivity. Furthermore, the integration of polymeric substrates may bring powerful advantages in comparison with silicon based ones. The biosensors will have a lower production costs being possible to disposable them after use ("one use sensor chip"). This research work represents a preliminary study about the influence of substrate temperature on the overall properties of ITO thin films deposited by DC magnetron sputtering onto 0,5 mm thick PMMA sheets.

JTD Keywords: ITO thin films, PMMA sheets, Waveguide biosensing devices, Biosensing devices, Conducting oxides, Dc magnetron sputtering, Electrochemical measurements, Enhanced performance, Innovative design, ITO thin films, Multilayer structures, Overall properties, PMMA sheets, Polymeric substrate, Production cost, Sensor chips, Silicon-based, Substrate temperature, Biosensors, Deposition, Design, Film preparation, Optical multilayers, Thin films, Vapor deposition, Waveguides, Substrates

The continuous flow focussing and manipulation of particles and cells are important factors in microfluidic applications for performing accurate and reproducible procedures downstream. Many particle focussing methods require complex setups or channel designs that can limit the process and its applications. Here, we present diamagnetic repulsion as a simple means of focussing objects in continuous flow, based only on their intrinsic properties without the requirement of any label. Diamagnetic polystyrene particles were suspended in a paramagnetic medium and pumped through a capillary between a pair of permanent magnets, whereupon the particles were repelled by each magnet into the central axis of the capillary, thus achieving focussing. By investigating this effect, we found that the focussing was greatly enhanced with (i) increased magnetic susceptibility of the medium, (ii) reduced flow rate of the suspension, (iii) increased particle size, and (iv) increased residence time in the magnetic field. Furthermore, we applied diamagnetic repulsion to the flow focussing of living, label-free HaCaT cells.

JTD Keywords: Feeble magnetic substances, On-chip, Blood-cells, Microfluidic device, Separation, Field, Levitation, Magnetophoresis, Fractionation, Nanoparticles

A ±1.2V / 350μW integrated front-end architecture for a true/false in-vivo subcutaneous detection device is presented. The detection is focused on using three electrodes amperometric sensors. The powering and AM transcutaneous communication are based on an inductively coupled link working at 13.56 MHz. A prototype device (5.5 mm x 29.5 mm) has been implemented and fully validated.

JTD Keywords: Implantable Device, Front-End architecture, Bioelectronics, Microelectronics Design, Biosensors

This work describes the data from navigation experiments with the mobile robot, equipped with the sensor array of three MOX gas sensors. Performed four series of measurements aim to explore the capabilities of sensor array to build the odour map with one or two odour sources in the wind tunnel space. It was demonstrated that the method based on Independent Component Analysis (ICA) is able to discriminate two odour sources, that in future can be used in the surge-and-cast robot navigation algorithm.

JTD Keywords: Mobile robots, Data acquisition, MIS devices, Chemioception

A biosensor is a detecting device that combines a transducer with a biologically sensitive and selective component. Biosensors can measure compounds present in the environment, chemical processes, food and human body at low cost if compared with traditional analytical techniques. This book covers a wide range of aspects and issues related to biosensor technology, bringing together researchers from 12 different countries. The book consists of 20 chapters written by 69 authors and divided in three sections: Biosensors Technology and Materials, Biosensors for Health and Biosensors for Environment and Biosecurity.

JTD Keywords: Bio-Devices, Electrochemical Instruments, Miniaturized Devices, Nanobiosensor

The importance of quality control in both general and respiratory medicine has increased in parallel with the complexity of healthcare provision. Only a few decades ago, the respiratory physician and/or scientist had a very limited number of diagnostic and therapeutic tools available and, moreover, medical practice was based almost exclusively on the personal interaction between doctor and patient. Consequently, at that time the quality of the respiratory healthcare depended entirely on the professional competence of the doctor. Although nowadays the relationship between physician and patient undoubtedly still lies at the heart of respiratory medical practice, the quality of the medical service received by the patient also depends on many other participants in a complex healthcare network: various medical specialists, lung function technicians, nurses, respiratory therapists, social workers and administrative staff. Accordingly, several quality control programmes are applied in order to avoid, or at least to reduce, errors in diagnosis, improper performance of procedures, errors in medication, and failure to supervise or monitor care or recognise complications associated with treatment

JTD Keywords: Airway pressure devices, Clinical-trial, Standardization, Spirometry, Lung, Home, Ventilators, Publication, Performance, Technology

Analytical devices able to perform accurate and fast automatic DNA detection or sequencing procedures have many potential benefits in the biomedical and environmental fields. The conversion of biological or biochemical responses into quantifiable optical, mechanical or electronic signals is achieved by means of biosensors. Most of these transducing elements can be miniaturized and incorporated into lab-on-a-chip devices, also known as Micro Total Analysis Systems. The use of multiple DNA biosensors integrated in these miniaturized laboratories, which perform several analytical operations at the microscale, has many cost and efficiency advantages. Tiny amounts of reagents and samples are needed and highly sensitive, fast and parallel assays can be done at low cost. A particular type of DNA biosensors are the ones used based on electrochemical principles. These sensors offer several advantages over the popular fluorescence-based detection schemes. The resulting signal is electrical and can be processed by conventional electronics in a very cheap and fast manner. Furthermore, the integration and miniaturization of electrochemical transducers in a microsystem makes easier its fabrication in front of the most common currently used detection method. In this review, different electrochemical DNA biosensors integrated in analytical microfluidic devices are discussed and some early stage commercial products based on this strategy are presented.

JTD Keywords: DNA, Electrochemical DNA biosensors, Electrochemistry, Lab-on-a-chip, Micro Total Analysis systems, Field-effect transistors, Sequence-specific detection, Chemical-analysis systems, Solid-state nanopores, Carbon nanotubes, Microfluidic device, Electrical detection, Hybridization, Molecules, Sensor